Introduction of antisense CD44S cDNA down-regulates expression of overall CD44 isoforms and inhibits tumor growth and metastasis in highly metastaticcolon carcinoma cells

Citation
N. Harada et al., Introduction of antisense CD44S cDNA down-regulates expression of overall CD44 isoforms and inhibits tumor growth and metastasis in highly metastaticcolon carcinoma cells, INT J CANC, 91(1), 2001, pp. 67-75
Citations number
43
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF CANCER
ISSN journal
0020-7136 → ACNP
Volume
91
Issue
1
Year of publication
2001
Pages
67 - 75
Database
ISI
SICI code
0020-7136(20010101)91:1<67:IOACCD>2.0.ZU;2-C
Abstract
We created antisense CD44 transfectants using LS174T, a colon adenocarcinom a cell line and assessed the effects of overall CD44 down-regulation on col orectal tumor growth and metastasis. The expression of antisense CD44s (the standard form of CD44) cDNA markedly inhibited the overall expression of C D44 variants. In vitro studies showed a significantly reduced ability of th e stable antisense transfectants (LS174TASI and LS174TAS2) to bind hyaluron ate and osteopontin, ligands for CD44, These cells developed tumors more sl owly than controls (parental LS174T and mock transfectants) when the cells were subcutaneously injected into SCID mice. However, in vitro proliferatio n assays demonstrated no significant difference between the antisense trans fectants and the controls on a hyaluronate-coated surface, suggesting the p articipation of ligands other than hyaluronate in tumor growth in vivo. Int rasplenic injection of parental LS174T cells produced colonies in the liver in 10 of 11 mice, whereas mice injected with the antisense transfectants w ere completely free of metastasis. In peritoneal dissemination, the weight of nodules and amount of ascites were significantly reduced in LS174TASI an d AS2 compared with the controls. In vitro adhesion assays between the tran sfectants or controls and human peritoneal mesothelial cells revealed that the binding of LS174T cells to mesothelial cells was partly mediated by CD4 4-hyaluronate interaction, These data suggest that: CD44-hyaluronate intera ction plays a crucial role in peritoneal dissemination in colorectal carcin oma. The results of our study demonstrate the possible application of antis ense CD44s to the treatment of colorectal carcinoma. (C) 2001 Wiley-Liss, I nc.